Traditional Tibetan medicine rhubarb formula granules and preparation method thereof

Abstract

The invention discloses a traditional Tibetan medicine rhubarb formula granule and a preparation method thereof, and aims to solve the problems of intolerance of patients to pharmaceutic adjuvants and medication of diabetic patients. The preparation method comprises the following steps: crushing rheum officinale, soaking in water, heating and extracting twice, filtering and concentrating to obtain an extract, mixing with raw rheum officinale powder in a ratio of 1: 1, and performing fluidized bed granulation. According to the method, auxiliary materials do not need to be added, the traditional decoction process is simplified, the extraction rate of effective components is increased, the exact drug effect is ensured, and meanwhile the requirements of special patients are met. The prepared granules are stable in character, the particle size and the moisture content both meet the standard, the content measurement result also meets the quality control requirement, and remarkable social benefits and economic benefits are achieved.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Tibetan medicine rhubarb formula granule and a preparation method thereof. Background Art

[0002] Tibetan medicine is a key component of traditional Chinese medicine. Based on this, Tibetan medicine has ushered in a new development opportunity, which also clarifies the direction for the development of Tibetan medicine in the new era. Tibetan rhubarb is a perennial dwarf herb of the Polygonaceae family and the genus Rheum, which occupies an important position in the field of Tibetan medicinal materials. As a traditional Chinese medicine with a long history and wide application, rhubarb has extremely significant effects. Rhubarb has the ability to remove blood stasis, can dredge the stagnant blood vessels in the body, and dissipate blood stasis clots. It has significant effects on blood stasis and swelling after trauma, as well as pain and numbness caused by blood stasis blocking the meridians.

[0003] As a unique preparation concept of traditional Chinese medicine, "combining medicine and excipients" occupies an important position in the long-standing Chinese medicine classics and classic prescriptions. In modern medicine, the common rhubarb formula granules in clinical practice are usually made by adding medicinal excipients. However, with the gradual attention paid to individual differences among patients, we found that some patients may show symptoms of intolerance to these medicinal excipients, such as allergic reactions or indigestion. Summary of the invention

[0004] The present invention aims to provide a traditional Tibetan medicine rhubarb formula granule and a preparation method thereof, so as to solve the problem of patients' intolerance to auxiliary materials and the problem of medication for diabetic patients.

[0005] To achieve the above object, the present invention provides the following technical solution: a traditional Tibetan medicine rhubarb formula granule and a preparation method thereof, comprising the following steps:

[0006] S1. Take an appropriate amount of rhubarb and crush it;

[0007] S2, soak in 10 times the amount of water for 30 minutes;

[0008] S3, heating extraction twice, the first time for 20 minutes, the second time for 15 minutes;

[0009] S4, filter, combine the filtrate, and concentrate to a density of 1.10-1.12 to obtain an extract;

[0010] S5. Add rhubarb powder that has passed through a No. 4 sieve, with the ratio of rhubarb paste to rhubarb powder being 1:1, and perform fluidized bed granulation.

[0011] Preferably, in step S5, the fluidized bed is set to have a spray speed range of 3 rpm to 16 rpm, a fan speed range of 600 rpm to 2100 rpm, a backblowing time of 1 second, an interval time of 20 seconds, an air inlet temperature not exceeding 110° C., a material temperature of not less than 43° C. during the granulation process, an end point air outlet temperature of not more than 45° C., and a granule moisture content of less than 8.0%.

[0012] The principle and beneficial effects of this technical solution:

[0013] (1) Improve the extraction rate of active ingredients: Through the extraction process, the extraction rate of active ingredients in rhubarb, such as rhubarb and chrysophanol, is improved. This optimization not only improves the efficacy, but also increases the utilization rate of rhubarb.

[0014] (2) Efficacy accuracy: The research results show that there is no significant difference in efficacy between rhubarb formula granules and herbal slices, which ensures the accuracy and significance of the efficacy and meets the various clinical needs for the use of rhubarb formula granules.

[0015] (3) Safety: Acute toxicity studies showed that there was no difference in toxicity between rhubarb formula granules and rhubarb slices.

[0016] (4) Meeting the needs of special patients: Considering that some patients are intolerant to pharmaceutical excipients, or diabetic patients are unable to take granules containing sucrose, the single-ingredient rhubarb granule formulation provided by the present invention does not require the addition of excipients, thereby meeting the needs of these special patient groups. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the process flow chart of rhubarb extraction;

[0018] Figure 2 The granulation process flow chart of rhubarb formula granules;

[0019] Figure 3 This is a thin layer identification diagram of rhubarb formula granules;

[0020] Figure 4 This is a comparison chart of the mixture of rhubarb and chrysophanol;

[0021] Figure 5 This is the liquid phase diagram of rhubarb formula granules;

[0022] Figure 6 It is the linear diagram of rhein;

[0023] Figure 7 This is the linear graph of chrysophanol. DETAILED DESCRIPTION

[0024] The present invention is further described in detail below with reference to the accompanying drawings and embodiments:

[0025] Example:

[0026] 1. Preparation

[0027] like Figure 1-2 As shown, take 100g of rhubarb, crush it, soak it in 10 times the amount of water for 30 minutes, and then heat and extract it twice, the first time for 20 minutes and the second time for 15 minutes. Filter, combine the filtrate, and concentrate it to a density of 1.10-1.12 to obtain an extract, add rhubarb powder that has passed through a No. 4 sieve, rhubarb paste and rhubarb powder in a ratio of 1:1, and perform fluidized bed one-step granulation to obtain it. Among them, the fluidized bed granulation parameters are: spray speed range: 3 rpm-16 rpm (adjusted according to the fluidization state); fan speed range: 600 rpm-2100 rpm (adjusted according to the fluidization state); set the back-blowing time to 1s, the interval time to 20s, set the inlet air temperature not to exceed 110℃ (80-100℃ is optimal), and when the material temperature range is not lower than 43℃ during the granulation process, the terminal outlet air temperature should be ≤45℃, and the particle moisture content is less than 8.0%.

[0028] 2. Properties

[0029] This product is yellow granules and tastes bitter.

[0030] 3. Identification

[0031] Take 0.1g of the powder of this product, add 20ml of methanol, soak for 1 hour, filter, take 5ml of the filtrate, evaporate to dryness, add 10ml of water to the residue to dissolve it, add 1ml of hydrochloric acid, heat and reflux for 30 minutes, cool immediately, shake and extract with ether twice, 20ml each time, combine the ether solution, evaporate to dryness, add 1ml of chloroform to the residue to dissolve it, and use it as the test solution. Take 0.1g of rhubarb reference medicinal material and prepare the reference medicinal material solution in the same way. Take the rhein reference substance again, add methanol to prepare a solution containing 1mg per 1ml, and use it as the reference substance solution. According to the thin layer chromatography method (General Rule 0502), 4 μl of each of the three solutions was taken and spotted on the same silica gel H thin layer plate with sodium carboxymethyl cellulose as the adhesive, and the upper layer solution of petroleum ether (30-60°C)-ethyl formate-formic acid (15:5:1) was used as the developing agent. The plate was developed, taken out, dried, and examined under ultraviolet light (365nm). In the chromatogram of the test sample, at the corresponding position of the chromatogram of the control medicinal material, the same five orange-yellow fluorescent main spots were shown as follows: Figure 3 shown.

[0032] 4. Granularity

[0033] According to the particle size and particle size distribution determination method (the second method of double screening method in the general rules of the fourth part of the 2020 edition of the Chinese Pharmacopoeia, 0982), the sum of the particles that cannot pass through the No. 1 sieve and the particles that can pass through the No. 5 sieve shall not exceed 15%. The determination results are shown in Table 3.

[0034] Table 1 Particle size test table of rhubarb formula granules

[0035]

[0036] The particle size measurement results of the above three batches showed that the particle size range of the rhubarb formula granules was 7.98% to 9.32%. According to the above measurement results, they all met the particle size limits of traditional Chinese medicine granules.

[0037] 5. Moisture

[0038] The moisture content of Chinese herbal medicine granules shall be determined according to the moisture determination method (General Rules 0832 of Part IV of the 2020 edition of the Chinese Pharmacopoeia). Unless otherwise specified, the moisture content shall not exceed 8.0%. The determination results are shown in Table 2.

[0039] Table 2 Moisture content test table of rhubarb formula granules

[0040]

[0041] The moisture content test results of the above three batches showed that the moisture content of the rhubarb formula granules ranged from 3.97% to 4.67%, and the moisture content test met the moisture content limit requirements of the pharmacopoeia granules.

[0042] 6. Determination of content of rhubarb formula granules

[0043] 6.1 Content determination method

[0044] According to the high performance liquid chromatography method (General Rules 0512 of Part IV of the 2020 edition of the Chinese Pharmacopoeia).

[0045] Chromatographic conditions: chromatographic column: C18 (4.6 mm × 250 mm, 5 μm); mobile phase: methanol-0.1% phosphoric acid solution (85:15); detection wavelength: 254 nm; column temperature: 30°C; flow rate: 1.0 mL·min-1; the theoretical plate number calculated based on the rhein peak should not be less than 2000.

[0046] like Figure 4-5 As shown, 1 is rhamnosin and 2 is chrysophanol. Preparation of reference solution: Take appropriate amount of rhamnosin reference substance and chrysophanol reference substance, weigh them accurately, and add methanol to prepare a solution containing 50 μg of rhamnosin per 1 mL and a solution containing 200 μg of chrysophanol per 1 mL, respectively.

[0047] Preparation of test solution: Take 0.5 g of the product, weigh it accurately, put it in a stoppered conical flask, add 10 mL of methanol accurately, weigh it, treat it with ultrasound for 30 minutes, let it cool, weigh it again, make up the lost weight with methanol, shake it well, filter it, and take the filtrate to obtain the solution.

[0048] 6.2 Methodological Study on the Content of Rhubarb Granules

[0049] 6.2.1 Investigation of linear relationship

[0050] like Figure 6-7 As shown, accurately measure the mixed reference solutions of emodin and chrysophanol in volumes of 1, 2, 4, 6, and 10 microliters, respectively. Determine the peak area according to the chromatographic conditions in item 6 of the Materials and Methods. The horizontal axis (x) is the concentration of the reference substance, and the vertical axis (y) is the peak area. Draw a standard curve and perform linear regression analysis to obtain the standard curve equation. The regression equation of emodin is Y = 3848.6X-1.6718, R2 = 1; the regression equation of chrysophanol is Y = 4558.2X + 23.572, R2 = 0.9999. Since the R 2 The values ​​are all greater than 0.999, which indicates that the method has a good linear relationship.

[0051] 6.2.2 Precision test

[0052] The test solution was accurately pipetted and the injection was repeated 6 times to determine the area of ​​​​rhaponticin and chrysophanol. The RSD of rhaponticin and chrysophanol was calculated to be 0.13% and 0.05% respectively. The test results are shown in Table 3.

[0053] Table 3 Precision test results of rhubarb samples

[0054]

[0055] 6.2.3 Stability test

[0056] Accurately pipette the test solution and pipette 10 μl of it for determination at 0, 4, 8, 18 and 24 hours according to the above chromatographic conditions. The test results are shown in Table 4.

[0057] Table 4 Stability test results

[0058]

[0059] The results showed that the peak areas of emodin and chrysophanol in the test solution were basically consistent within 24 hours, and their RSDs were calculated to be 1.14% and 1.46%, respectively, indicating that the test solution was stable within 24 hours.

[0060] 6.2.4 Reproducibility test

[0061] Six samples from the same batch were taken to prepare test solutions, and the results showed that the average mass fractions of emodin and chrysophanol were 0.021 mg·g －1 , 0.082mg·g －1 , RSDs were 0.95% respectively.

[0062] 6.2.5 Sample recovery test

[0063] Weigh 0.5g of rhubarb formula granules accurately, a total of 6 portions, accurately add 50mg·L-1 of rhubarb and 200mg·L-1 of chrysophanol, 2mL of reference solution, and then accurately add 8mL of methanol, ultrasonically treat for 30min, make up the lost weight with methanol, filter, take the filtrate, inject and measure, and calculate the recovery rate. The test results are shown in Table 5.

[0064] Table 5. Sample recovery test results

[0065]

[0066] 6.2.6 Sample determination

[0067] Three batches of samples were taken, 0.5 g each, and the test solutions were prepared respectively, and the test results were performed according to the proposed content determination method. The test results are shown in Table 6.

[0068] Table 6 Determination results of the content of rhubarb and chrysophanol in 0.5g of rhubarb formula granules

[0069]

[0070] 7. Results Analysis

[0071] Through the examples, the preparation process of rhubarb formula granules includes the steps of crushing, soaking, extraction, filtering, concentration and granulation. This process is optimized on the basis of the traditional decoction process, and by adding rhubarb raw powder, the preparation of granules without adding auxiliary materials is realized. The prepared granules are yellow and bitter, which is consistent with the natural characteristics of rhubarb, indicating that the preparation process retains the main characteristics of rhubarb.

[0072] The rhubarb formula granules were identified by thin layer chromatography. The results showed that the same five orange-yellow fluorescent main spots appeared at the corresponding positions in the chromatogram of the test sample and the control medicinal material, indicating the presence of the active ingredients in the rhubarb formula granules. The particle size test results showed that the particle size range of the rhubarb formula granules was 7.98% to 9.32%, which met the requirements of the particle size limit of Chinese medicine granules, and the consistency and controllability of the granulation process. Moisture content: The moisture content test results showed that the moisture range of the rhubarb formula granules was 3.97% to 4.67%, which was lower than the upper limit of 8.0% specified in the pharmacopoeia, indicating that the degree of drying of the granules was appropriate, which was conducive to storage and maintaining the efficacy. High performance liquid chromatography was used to determine the content of rhubarb and chrysophanol. The results showed that the content of rhubarb should not be less than 0.15% and the content of chrysophanol should not be less than 0.5%, which provided quantitative indicators for the quality control of rhubarb formula granules.

[0073] Common clinical rhubarb granules are made by adding pharmaceutical excipients. Considering that some patients may be intolerant to some pharmaceutical excipients, or diabetic patients cannot take granules containing sucrose, this institute has developed a single-flavor rhubarb formula granule. On the basis of the traditional decoction process, rhubarb raw powder is added to make rhubarb granules without excipients, which can realize automatic adjustment and mechanized decoction for hospital pharmacies, shorten the time for patients to wait for medicine, and thus reduce the burden of Chinese medicine pharmacy packaging and adjustment, and facilitate patients to meet market demand. The results of the embodiment show that the preparation method of rhubarb formula granules is scientific and reasonable, the product properties are stable, the identification is accurate, the particle size and moisture content meet the standards, and the content determination results also meet the quality control requirements. It provides research ideas for the preparation of granules without adding excipients for single-flavor medicines, and provides experimental basis for the formulation of quality standards for single-flavor medicine granules in the future.

[0074] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions or characteristics in the solution is not described in detail here. For those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A traditional Tibetan medicine rhubarb formula granule and its preparation method, characterized in that: The following steps are involved: S1. Take an appropriate amount of rhubarb and crush it; S2, soak in 10 times the amount of water for 30 minutes; S3, heating extraction twice, the first time for 20 minutes, the second time for 15 minutes; S4, filter, combine the filtrate, and concentrate to a density of 1.10-1.12 to obtain an extract; S5. Add rhubarb powder that has passed through a No. 4 sieve, with the ratio of rhubarb paste to rhubarb powder being 1:1, and perform fluidized bed granulation.

2. A traditional Tibetan medicine rhubarb formula granule and its preparation method according to claim 1, characterized in that: The fluidized bed granulation parameters are as follows: in step S5, the fluidized bed is set to have a spray speed range of 3 rpm to 16 rpm, a fan speed range of 600 rpm to 2100 rpm, a back-blowing time of 1 second, an interval time of 20 seconds, an air inlet temperature not exceeding 110° C., a material temperature of not less than 43° C. during the granulation process, an end point air outlet temperature of not more than 45° C., and a granule moisture content of less than 8.0%.

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